HOUSTON (Sept 27, 2010) Baylor College of Medicine — Physicians and scientists at Baylor College of Medicine and the Texas Children’s Cancer Center are pioneering research to improve the treatment and outcomes for pediatric cancer patients who have cancers with poor survival rates.

Research on Osteosarcoma

Lisa Wang, M.D.

Dr. Lisa Wang, assistant professor of pediatrics – hematology/oncology at BCM, is director of the Bone Tumor Program at the Texas Children’s Cancer Center. Her research focuses in part on metastatic osteosarcoma, which has a survival rate of less than 25 percent.

“There really have been no advances in treatment and survival for this type of cancer in the last 30 years,” Wang said. “There is an urgent need to develop novel therapies for patients with metastatic osteosarcoma.”

Multidisciplinary team approach

A recent $3.7 million grant over three years from the Cancer Prevention and Research Institute of Texas brings together experts in pediatric oncology, molecular cancer biology, genomics, proteomics, immunotherapy and cancer animal models who are committed to studying and treating osteosarcoma.

“Their expertise will be applied to three projects that alone have intrinsic importance to the field of OS research, but together will contribute even more to the discovery, analysis, preclinical and clinical testing of novel therapeutic targets for metastatic osteosarcoma,” Wang said.

Three projects

Project 1 will generate novel mouse models of metastatic OS to investigate critical genetic events important for metastasis (spreading of cancer to other organs in the body). Project 2 will utilize high-throughput sequencing to identify novel biomarkers of metastatic potential and to potentially identify new therapeutic targets. Project 3 will focus on immunotherapy to treat osteosarcoma. Specifically, it will evaluate the treatment potential of HER2-specific T-cells, which have been shown to have a potent anti-tumor effect in animal models. The protein HER2 is expressed in about 60 percent of osteosarcoma tumors.

Wang is collaborating with researchers at Baylor College of Medicine, the University of Texas M. D. Anderson Cancer Center and Texas A&M University.

She also received a $1.125 milion grant from the National Institutes of Health to research the role of the gene RECQL4 in the development of osteosarcoma and other bone diseases, such as osteoporosis.

This project will study patients with Rothmund-Thomson syndrome (RTS), a human genetic disorder. RTS patients have a higher incidence of osteosarcoma, and researchers have found that they have mutations in the gene REQCL4. In this study, Wang will collaborate with Dr. Brendan Lee, BCM professor of molecular and human genetics, on research using mouse models with REQCL4 deficiency to develop a better understanding of the role of the gene in bone disease and bone cancer.

“This will allow us to discover novel ways to improve the treatment of osteosarcoma and osteoporosis in the general population,” Wang said.

Research on brain cancer

Like osteosarcoma, some brain cancers also have a poor survival rate. Dr. Donald “Will” Parsons, BCM assistant professor of pediatrics – hematology/oncology, has focused much of his research on the genomic analysis of brain tumors, working in collaboration with BCM’s Human Genome Sequencing Center.

“We still don’t do very well curing kids with certain types of brain cancer,” he said. “The survival rate for some specific types is close to zero.”

Glioma

Glioma is one type of brain cancer with a low survival rate. Parsons recently received a grant from the Doris Duke Foundation that will support his goal of identifying genetic mutations or deletions that lead to gliomas.

“Because of the advances in genome sequencing that have been made over the last decade, for the first time we have the capability to sequence genes on a large scale to determine to determine what some of these mutated genes are that are causing cancer,” Parsons said. “This may enable us to come up with specific medicines and treatment rather than using the same, nonspecific treatment for all brain cancers.”

New targeted therapy is especially important for brain tumors because of the side effects of standard treatment, which typically includes chemotherapy and radiation. Many children with brain cancer are very young, and their brains are still developing. The effects of treatment can be very profound, Parsons said.

Even children with brain cancers that have a higher cure rate, such as medulloblastoma, may fall into a category of patients who do not respond well to treatment, Parsons said.

Goal of research

An overall goal of his work is to determine through genetic research the underlying reason why a patient does or does not respond to treatment. This too, will help scientists develop potential targeted therapies.

Parsons also received a CPRIT grant to study liver tumors in pediatric cancer and is engaged in similar genomic analyses of several other pediatric solid tumors.

Research on genetic susceptibility

Dr. Sharon Plon, professor of pediatrics – hematology oncology, is also taking advantage of advances in gene sequencing in her research.

Her research focuses on DNA sequencing to find gene mutations that make families susceptible to pediatric cancer.

Who’s at risk?

“We’ll be using the newest technology to understand why some families are more at risk,” Plon said. “People want to understand why this happens to their family, and we want to be able to provide those answers.”

She is currently working on a CPRIT-funded study that will examine people who have had more than one cancer – for example, a childhood cancer and a second malignancy later in life – and those who have cancer history in their extended family.

Another project funded by the National Cancer Institute will include families where siblings have both been diagnosed with cancer as well as children diagnosed with cancer who also have other birth defects and learning disabilities to identify gene mutations that contribute to these susceptibilities.

Cancer susceptibility syndrome

Plon has also been involved with Dr. Lisa Wang in research on Rothmund-Thomson syndrome, which is a cancer susceptibility syndrome. They have previously shown that RTS patients who develop osteosarcoma carry deleterious mutations in the RECQL4 gene and her group has identified certain disease-causing mutations that are associated with mislocalization of the RECQL4 protein.

About Texas Children's Cancer and Hematology Centers

As an international leader in pediatric cancer research and treatment, Texas Children’s Cancer and Hematology Centers are joint programs of Texas Children's Hospital and Baylor College of Medicine. The Centers are dedicated to providing novel therapies and family-centered care to children from infancy through young adulthood with cancer and blood disorders – from the most common to very rare. Texas Children’s Cancer Center is the pediatric program of BCM’s NCI-designated Dan L. Duncan Cancer Center.
Ranked by U.S. News & World Report as the #2 Center in the United States, Texas Children’s Cancer and Hematology Centers treats more childhood cancer and hematology patients than any other program in the U.S., with patients coming from 35 states and 26 countries around the world.